DESCRIPTION: The objective is to search for mechanisms by which the female hormones progesterone and estrogen influence vaginal transmission and pathogenesis of SIV in rhesus macaques. In work recently published by this laboratory, progesterone was shown to increase SIV vaginal transmission and thinning of the vaginal epithelium was proposed as one potential mechanism. However affects on immune responses, possible increases in target cells within vaginal tissues, or direct effects on in vivo SIV replication were not studied and are the object of this new application. Specific aim one individually tests the effects of progesterone and estrogen on SIV vaginal transmission, pathogenesis, and virus-specific immune responses. Specific aim two tests progesterone and estrogen effects on in vivo pathogenesis after intravenous infection of hormone treated macaques. These studies allow evaluation of two hormones important for female reproductive cycles and allow the study of ovariectomized animals to isolate the effects of virus transmission independent of these hormones. The studies should inform about the potential hazards of female contraceptives and how they may influence virus transmission. In addition basic information will be provided on the effects of female reproductive hormones on virus transmission and viral pathogenesis.